tbuckley/cabot-search huggingface dataset:
Abstract 4698: Reproducibility in spatial biology: reducing variables to improve the reliability of insight generation
Authors: Lisa Arvidson, Reginaldo Prioli, Samuel Jensen, James B. Hoying, Michael W. Golway, Michael J. Smith, Katie O. White, Richard A. Heil-Chapdelaine, Chi-Chou Huang, Tuan H. Phan, Hideki Sasaki, Melinda Angus-Hill
Journal: Cancer Research (2023)

Abstract There is an ongoing crisis in reproducibility in scientific studies, and studies in spatial biology are no exception. Cell DIVETM Multiplex imaging solution (Leica Microsystems) provides reliable workflow solutions to minimize variability from study to study. Cell DIVE allows probing and imaging of dozens of biomarkers on a whole tissue section with an iterative staining and dye inactivation workflow. At its core, Cell DIVE is designed to provide methods reproducibility, from tissue preparation, antigen retrieval, and sample imaging and slide storage. Cell DIVE is designed to work with directly conjugated primary antibodies, another source of variability. However, conjugated antibodies from Cell Signaling Technology (CST) are rigorously validated using stringent acceptance criteria to reduce variability. In addition, the use of recombinant antibodies, the consistent conjugate brightness and antibody degree-of-labeling reduce lot to lot variability, ensuring reliable conjugated antibodies for spatial biology studies. High resolution imaging results are obtained by consistent round to round imaging, consistent calibration and corrections, and reduction of human error using the BAB 200 liquid handling solution (Advanced Solutions Life Sciences). We present here, an iterative biomarker study using adjacent tissue sections probed with distinct lots of CST antibody panels, imaged in temporally separated batches using a Cell DIVE imager fitted with a BAB200 liquid handler. Following robust analysis (segmentation, phenotyping and statistical analysis), we report the reproducibility findings across parameters. Methods and results reproducibility in spatial biology is essential for reliable insight generation, giving confidence in the quality of future studies aimed at improving patient outcomes. Citation Format: Lisa Arvidson, Reginaldo Prioli, Samuel Jensen, James B. Hoying, Michael W. Golway, Michael J. Smith, Katie O. White, Richard A. Heil-Chapdelaine, Chi-Chou Huang, Tuan H. Phan, Hideki Sasaki, Melinda Angus-Hill. Reproducibility in spatial biology: reducing variables to improve the reliability of insight generation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4698.
Abstract 6531: Point of care test for cervical cancer screening
Authors: Samrin Farouk Idris Habbani, Sayeh Jalali Dowlatshahi, Monisha Elumalai, Scott Charles Bolton, Lucy Teberh Tecle, Pankti Rajesh Thakkar, Jacqueline C Linnes, Sulma I Mohammed
Journal: Cancer Research (2023)

Abstract Cervical cancer is a lethal gynecological malignancy and the fourth most common cancer among women. Most high-grade cervical pre-cancers and cancer cases are linked to infection with high-risk human papillomaviruses (HPV). There is an inequity between high-income countries (HICs) and low- and middle-income countries (LMICs) in cervical cancer burden; according to the World Health Organization, the estimated mortality rate of cervical cancer is 342,000 women worldwide in 2020, and 90% of these women reside in low- and middle-income nations where the human papillomavirus vaccine is unavailable and access to early detection testing are either unavailable or too expensive. This study aims to develop a simple and affordable point-of-care test based on four critical biomarkers for screening high-risk pre-cancer and invasive cervical cancer in collaboration with the biomedical engineering department. A cervical cancer swab will be used in the test. The swab will be placed on a paper-based device that looks for four protein biomarkers critical for the progression of noninvasive cervical cancer into invasive cervical cancer by combining two approaches using proteomics and lateral flow immunochromatography technology. We have validated the markers' expression in cervical cancer and precancerous tissues. The four markers were expressed in squamous cell carcinoma, glassy cell carcinoma, adenocarcinoma, clear cell carcinoma cancer tissues, and the high-grade cervical intraepithelial neoplasia. This point-of-care test will be affordable and implementable, especially in low and middle-income countries. Citation Format: Samrin Farouk Idris Habbani, Sayeh Jalali Dowlatshahi, Monisha Elumalai, Scott Charles Bolton, Lucy Teberh Tecle, Pankti Rajesh Thakkar, Jacqueline C Linnes, Sulma I Mohammed. Point of care test for cervical cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6531.
Abstract 2246: Prevalence of mycobacterium tuberculosis among PAP smear samples of cervical cancer suspects
Authors: Wondimu Ashagre Awoke
Journal: Cancer Research (2023)

Abstract Introduction: Cervical cancer is one of the most common cancers in women around the world. The Pap smear test is the most common method of detecting abnormal cells that may develop into cancer. In addition, we want to know how common mycobacterium tuberculosis is among those who provide Pap smear samples. Objectives: The purpose of this study is to examine the knowledge, attitudes, and practices of working women in Addis Abeba, Ethiopia, regarding cervical cancer and Pap smear tests, as well as the associations between knowledge, attitudes, and practices and socio-demographic factors. In addition, we will investigate the prevalence of mycobacterium tuberculosis from smears among those who provide Pap smear samples. Methods: This will be a cross-sectional questionnaire-based study of 100 Ethiopian females' attending at Arsho medical laboratories from September to December 2022, knowledge, attitudes, and practices, as well as the prevalence of tuberculosis. All women between the ages of 20 and 65 who wanted to be diagnosed with cervical cancer were eligible. Expected outcome: To teach and recall common cervical cancer symptoms such as menstrual bleeding, the appropriate age for Pap smear tests, and the interval between tests. Examine their use of hormonal contraception and their attitude toward Pap smear testing over the last five years. It will also be useful to know the prevalence of cervical tuberculosis. Citation Format: Wondimu Ashagre Awoke. Prevalence of mycobacterium tuberculosis among PAP smear samples of cervical cancer suspects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2246.
Abstract 140: Clonal evaluation of ERG/SPINK1 status to determine disease progression using whole mount prostatectomy specimens
Authors: Joonyoung Cho, In Hye Suh, HyeYoon Chang, Tae-Yeong Kwak, Sun Woo Kim, Nallasivam Palanisamy
Journal: Cancer Research (2023)

Abstract Most primary prostate cancers are multifocal, marked by distinct tumor foci. Multiclonality is not routinely incorporated at clinical evaluation, however, marker status as a pathological parameter holds great potential for improving prognostic accuracy. Here, we evaluated the frequency of multiclonality and whether ERG/SPINK1 status is correlated to aggressive disease in whole-mount specimens. For each of the 89 radical prostatectomy cases, one H&amp;E-stained whole-mount slide and a corresponding dual ERG/SPINK1 IHC stained slide were collected. Aperio AT2 scanner (Leica Biosystems) digitized these slides into whole-slide images (WSIs). All WSIs were reviewed by a pathologist with the aid of an automatic Gleason grading software to identify each tumor focus and determine its Gleason grade group (GG), and the expression levels (% uptake) of ERG and SPINK1, respectively. Grade groups 4 and 5 were treated as one high-grade group (GG4-5). The associations among GG, ERG, and SPINK1 expression levels were analyzed. For each WSI, 1 to 7 (median 2, mean 2.53) tumor foci were identified, and the aforementioned values were determined, resulting in 225 data records. The number of tumor foci, ERG/SPINK1 expression statistics, and their association for each GG are shown in the table. ERG was expressed the most frequently in GG1, and its frequency decreased as the grade increased. Conversely, SPINK1 expression frequency increased with the grade group. The expression of ERG and SPINK1 was inversely correlated regardless of grade group. More detailed results on the exploratory data analysis and the association with BCR will be shared at the time of presentation. ERG or SPINK1 expression do not appear to be associated with Gleason grade groups. More studies are needed to see if these markers may predict recurrence free survival or patient response to therapy. To our knowledge, this is the first study to map molecular subtypes in whole-mount samples utilizing a foci-based approach. Table Grade group Total ERG SPINK1 ERG-SPINK1 positive ratio (%) positive ratio (%) co-positive co-negative mutually exclusive GG1 74 38 51.4 24 32.4 4 16 54 GG2 81 35 43.2 40 49.4 7 13 61 GG3 33 11 33.3 22 66.7 4 4 25 GG4-5 37 10 27.0 13 35.1 1 15 21 Overall 225 94 41.8 99 44.0 16 48 161 Citation Format: Joonyoung Cho, In Hye Suh, HyeYoon Chang, Tae-Yeong Kwak, Sun Woo Kim, Nallasivam Palanisamy. Clonal evaluation of ERG/SPINK1 status to determine disease progression using whole mount prostatectomy specimens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 140.
Abstract 1990: Targeting cancer stem cells is an answer to the curing lung cancer
Authors: Keum-Soo Song, Satish Balasaheb Nimse, Taisun Kim
Journal: Cancer Research (2023)

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Mainly, non-small cell lung cancer (NSCLC, about 80% of cases) and small cell lung cancer (SCLC, about 20% of cases) are the major types of lung cancer. Adenocarcinoma (30-50%) and squamous cell carcinoma (30%) are the major subtypes of NSCLC. Even though there are considerable advancements in the drugs against lung cancer, the 5-year survival rate is meager. Unfortunately, the drug resistance for currently available anticancer drugs results in a 5-year survival of only 5%. The remarkable lung cancer recurrence despite definitive local and/or systemic therapy indicate that residual cancer stem cells (CSCs) possess tumorigenic potential. Therefore, drugs targeting the CSCs and killing them quickly can cure lung cancer without any relapse and improve the 5-year survival rate. Herein, we present the application of the recently reported ID-Checker technology (Journal of Medicinal Chemistry 2022 65 (19), 12883-12894) for killing lung cancer stem cells (LCSC). The ID-Checker that is decorated with the glucose tag allows highly specific absorption and macroscale delivery of anticancer drugs to the LCSC through the GLUT channels. ID-Checker inhibits the microtubule formation resulting in the cell cycle arrest in the G2/M phase followed by apoptosis. The inhibition of microtubule formation by ID-Checker also leads to the inhibition of GLUT channel deployment in the LCSC. Thus, the glucose-deprived LCSC undergoes apoptosis within 72 hours of ID-Checker treatment. Hence, we believe the ID-Check technology presented here can kill the LCSC and completely cure lung cancer. Citation Format: Keum-Soo Song, Satish Balasaheb Nimse, Taisun Kim. Targeting cancer stem cells is an answer to the curing lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1990.
Abstract 5582: Liquid biopsy-based comprehensive genomic profiling reveal mutational landscape in real-world patients with unresectable NSCLC
Authors: Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia
Journal: Cancer Research (2023)

Abstract Introduction: NSCLC accounts for more than 80% of all lung cancer, and has been shown for clinical benefits from targeted therapies, according to tests of multiple genes, such as EGFR, KRAS, ALK, ERBB2. Previous studies revealed molecular characteristics and responses of targeted therapies in NSCLC. However, most studies used tissue biopsies. There is increasing interest to characterize the molecular profile of NSCLC through liquid biopsy. Hence, here we report a comprehensive genomic profiling study in unresectable NSCLC patients using liquid biopsy. Methods: The prospective study is part of the Predicine’s Phoenix Program, a global molecular biomarkers screening program in multiple solid tumors. Currently, the study enrolled 352 unresectable advanced NSCLC patients from 24 centers in China, who were naïve to the 1st line treatment or recurrent after 1st line targeted therapies. 10ml of blood was collected from each patient and delivered to a central lab for ctDNA analysis. The study applied PredicineCARE, an NGS-based liquid biopsy assay, to profile somatic mutations, copy number variations, and gene fusions among these patients. Results: The study identified 1614 somatic mutations and 202 copy number variants among blood samples from 352 patients. The most common altered genes were TP53(176/352, 50%), EGFR(144/352, 41%), PIK3CA(35/352, 10%), CDNK2A(35/352, 10%), KRAS(28/352, 8%), and RB1(28/352, 8%). Gene copy number gain incidents were identified on MYC(n=22), PIK3CA(n=16), EGFR(n=15), and MET(n=7), etc. Notably, the study also reported gene copy number loss incidents through liquid biopsy, such as CDKN2A(n=16), PTEN(n=11), and RB1(n=10). The study identified 12 gene fusion incidents, including 7 EML4-ALK fusions, 2 RET fusions(KIF5B-RET and NCOA4-RET), 2 NTRK fusions(ETV6-NTRK3 and NOS1AP-NTRK1), and 1 rare CD74-NRG1 fusion. Conclusions: This study revealed the comprehensive mutational landscape of advanced NSCLC through liquid biopsy, providing novel biomarkers for clinical diagnosis and targeted therapy mechanism studies. Citation Format: Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia. Liquid biopsy-based comprehensive genomic profiling reveal mutational landscape in real-world patients with unresectable NSCLC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5582.
Abstract 5051: Assessment of boron delivery peptides with angiopep-2 for boron neutron capture therapy
Authors: Qi Liu, Jing Xiang, Lin Ma, Qiushi Ren
Journal: Cancer Research (2023)

Abstract Boron neutron capture therapy (BNCT) induces intracellular nuclear reactions that release heavy charged particles to destroy cancer cells during thermal neutron radiation. In order to selectively eliminate cancer cells but avoid harmful effects to normal tissues, targeted delivery of boron-10 in cancer cells is required, whereas the conventional boron delivery agent phenylalanine (BPA) is unsatisfactory. Angiopep-2 is a cell-penetrating peptide that can trigger transcytosis and traverse the blood-brain barrier by recognizing low density lipoprotein-related protein 1. In this study, we developed angiopep-2 for boron delivery in BNCT. Angiopep-2 was labeled with boron-10 using solid-phase peptide synthesis with 4-carboxyphenylboronic acid and fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids, namely ANG-B. Molecular mass of the synthesized ANG-B were validated by mass spectrometry. In a cell proliferation assay, little toxicity of ANG-B was detected. Boron concentrations in 6 cell lines from different cancer types and an intracranial glioblastoma mouse model after treatment with ANG-B or BPA were analyzed by ICP-AES. The in vivo distribution of ANG-B showed that the ratio of boron content of tumor tissue to that of blood (T/B ratio) was 9.42±2.47 at 4h post treatment, while the ratio of boron content of tumor tissue to that of normal brain tissue (T/N ratio) was 5.61±1.0, demonstrated an optimal tumor targeting ability of ANG-B. We further measured the effects of ANG-B in BNCT by clonogenic cell survival assay in vitro or by PET/CT imaging on a glioblastoma mouse model in vivo. Radiation for BNCT was given with neutron flux at 3.0±0.4 × 1011 n/cm2. BNCT with 5 mM ANG-B resulted in 86.5%±5.3% clonogenic cell death, while the number was 72.9%±5.1% for BPA. The effect of ANG-B based BNCT in vivo was also better than BPA. The glioblastoma tumors in ANG-B treated group at 31 days after BNCT were shrank by 62.9% in average, while the BPA treated tumors shrank by only 23.0% (P&amp;lt;0.05). Therefore, we concluded that ANG-B is an efficient boron delivery agent, which may improve BNCT performance in clinical trials. Citation Format: Qi Liu, Jing Xiang, Lin Ma, Qiushi Ren. Assessment of boron delivery peptides with angiopep-2 for boron neutron capture therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5051.
Abstract 1352: SOX17 plays a critical role in immune evasion of colorectal cancer
Authors: Norihiro Goto, Saori Goto, Peter Westcott, Shinya Imada, Judith Agudo, Omer Yilmaz
Journal: Cancer Research (2023)

Abstract Colorectal cancers (CRCs) are a leading cause of cancer-related death. Most CRCs are immune cold, and do not respond to checkpoint blockade therapy except for microsatellite-high CRCs harboring high mutational burdens. Deciphering the mechanism by which CRC cells evade immune surveillance has the potential to dramatically improve the prognosis of CRC patients. During tumor evolution of CRCs, epigenetic changes play critical roles in addition to accumulation of genetic mutations. However, distinct mutational patterns and patient backgrounds render it challenging to distinguish the driver epigenetic alterations from passenger epigenetic alterations induced by gene mutations or other environmental factors. Identification of the driver epigenetic alterations may provide novel mechanistic insights into colon cancer biology including how they evade immune surveillance. Here, we utilized the colon cancer organoid orthotopic transplantation approach to establish colon cancer organoids from different stages of the tumors, and performed comprehensive epigenomic and transcriptomic analyses to understand the epigenetic alterations during tumor evolution. We found that in vivo environment induces epigenetic alterations that converge on SOX17, a transcription factor that is required for endoderm development. SOX17 is re-expressed in colon cancers in vivo, but not in the in vitro organoid culture, and reprograms tumor cell fate with fetal intestinal gene expressions. Importantly, SOX17 knockout leads to tumor rejection in immunocompetent mice, but not in immunodeficient mice, by turning immune cold tumors into hot tumors with robust intratumoral infiltration of activated CD8+ T cells. Mechanistically, SOX17 directly downregulates Ifngr1 expression and mitigates MHC-I expression to evade CD8+ T cell-mediated tumor cell killing. Together, our result reveals that SOX17 is a master transcription factor that induces the in vivo epigenetic reprograming of tumors, which contributes to the immune evasion of colon cancers. Citation Format: Norihiro Goto, Saori Goto, Peter Westcott, Shinya Imada, Judith Agudo, Omer Yilmaz. SOX17 plays a critical role in immune evasion of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1352.
Abstract 2759: Real-time cellular target engagement and protein quantification for drug discovery
Authors: Ivan Babic, Nikolas Bryan, Claire Cunningham, Avery Sampson, Daniel Starczynowski, Elmar Nurmemmedov
Journal: Cancer Research (2023)

Abstract Preclinical assessment of direct drug-target engagement and analysis of binding kinetics within the cellular environment is essential for development of safer and more effective therapeutics. Infusion of such critical data into early drug discovery would significantly reduce the failure rate of new drug candidates, accelerate drug discovery, and validate repurposing of existing drugs. Described here is a novel drug-target engagement technology that can sensitively interrogate direct binding of drugs to cellular, bacterial, or viral protein targets within the physiological environment. Micro-Tag cell target engagement technology is based on complementation of a small 15-amino acid subunit with a large subunit into an active RNA-processing enzyme. The small subunit can be cloned to any drug target for transient or stable expression using existing tools such as CRISPR. Upon complementation, the active enzyme cleaves a FRET-based oligonucleotide substrate resulting in rapid generation of fluorescent signal that can be quantified in real time. The Micro-Tag technology enables in-cell quantitation of drug target levels using qPCR systems. This is the next-generation of target engagement technology that allows for real-time monitoring of drug-target interaction in the cell. We show here data demonstrating direct engagement of several reference compounds and novel small molecules with high-profile cancer targets such as K-RAS, MTH1, EGFR, and UBE2N. Selectivity of these drugs to the targets in the cell is further delineated using their mutant counterparts as well as inactive stereoisomer compounds. The Micro-Tag cell target engagement technology provides the power of cell target engagement to a large family of target proteins. It can be employed for high-throughput screens directed at initial on-target ranking or med-chem optimization of drug candidates. It is amenable for interrogation of drug candidates across various modalities: small molecules, peptides, antibodies and PROTACs. Importantly, this next-generation target engagement technology seamlessly integrates with qPCR systems, fluorescence microscopy, live-cell microscopy, FACS analysis, and offers multiplexing capability, thus allowing for further mechanistic insight. Citation Format: Ivan Babic, Nikolas Bryan, Claire Cunningham, Avery Sampson, Daniel Starczynowski, Elmar Nurmemmedov. Real-time cellular target engagement and protein quantification for drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2759.